Chuprina V P, Lipanov A A, Kim S G, Kintanar A, Reid B R
Research Computer Center, U.S.S.R. Academy of Sciences, Pushchino, Moscow Region.
Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9087-91. doi: 10.1073/pnas.88.20.9087.
Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1' protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1' distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 A depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is greater than 4.5 A. In GA steps, x varies within rather wide limits in the range 3.8-4.5 A, whereas in AA steps the lower limit is 3.7 A and the upper limit is approximately 4.2 A. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5' end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3' end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3' end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B' structure when the substitution produces an AnTm tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1' distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1' distances depending on the DNA sequence. By using high-resolution x-ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1'-H1'. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs.
给出了几种不同DNA双链体中，同一条链或互补链上腺嘌呤H2质子与异头H1'质子之间通过核Overhauser效应得出的距离。跨链（n）AH2至（m + 1）H1'的距离[表示为x，其中（n）和（m）是互补残基]根据序列的不同变化可达1埃。在所有可能含A的嘧啶-嘌呤步（CA、TG和TA）中，x大于4.5埃。在GA步中，x在3.8 - 4.5埃的相当宽范围内变化，而在AA步中，下限是3.7埃，上限约为4.2埃。在嘌呤-嘌呤步中，x受至少三个因素影响：（i）5'端相邻的嘧啶-嘌呤步[例如，YRA序列（其中Y = T或C，R = G或A）]，或互补链上嘧啶-嘧啶步3'端的嘧啶-嘌呤步，会使x增大；（ii）嘌呤-嘌呤步3'端的AT步（例如，RAT）会使x减小；（iii）次近邻位置碱基的取代会导致GA和AA步中x的变化。后一个因素似乎是由于当取代产生AnTm片段（这总是会使x减小）时形成“异常”B'结构所产生的协同效应。数据表明，同一条链上（n）AH2 - （n + 1）H1'的距离（表示为s）也依赖于序列。因此在AA步中，相邻取代对s的影响与对跨链x距离的影响相同。这些结果使得能够根据DNA序列预测AH2 - H1'距离的变化。通过使用高分辨率x射线B型结构作为一组允许的B构象，发现x与小沟宽度参数P - P或H1' - H1'之间有很好的相关性。因此，x距离是B型DNA中小沟宽度的直接探针，该距离的变化因此反映了小沟宽度的变化。由于所研究的许多序列是蛋白质识别位点，DNA中观察到的序列-结构依赖性可能在蛋白质和小沟配体（如药物）的识别过程中起重要作用。
